The goal of newborn screening is to detect potentially fatal or disabling conditions in newborns, thereby providing a window of opportunity for early treatment, often while the child is still asymptomatic. Such early detection and treatment can have a profound impact on the clinical severity of the condition in the affected child. If left undiagnosed and untreated, the consequences of the targeted disorders can be dire, many causing irreversible neurological damage, intellectual, developmental and physical disabilities, and even death. In 2006, the American College of Medical Genetics (ACMG) developed newborn screening guidelines that recommend that all newborn infants be screened for 31 core conditions and that 26 secondary conditions identified during the core evaluations be reported. These recommendations have been accepted by the HHS Secretary's Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC) (authorized by the Children's Health Act of 2000), and by the Secretary of HHS. Most states now use this or very similar panels for newborn screening. Currently, there are thousands of rare disorders that have been identified and hundreds that could potentially benefit from newborn screening. It has become evident however, that a major impediment to implementing new technologies in high throughput newborn screening laboratories is the ability to provide evidence of the feasibility of the assay, both scientifically and logistically, in a timely manner. A majority of disorders considered for newborn screening are rare diseases where the likelihood of detecting cases during standard newborn screening in a single laboratory is very low. For this reason collaborative efforts, implemented across multiple states or newborn screening laboratories, are necessary for the successful development and implementation of new assays and the addition of new conditions to the Recommended Uniform Screening Panel (RUSP).